OBJECTIVE: To examine the effects of the NMDA antagonist MK801 on the antisense GAD67-induced LHRH increase. RESULTS Previously, we showed that the reduction of GABA inhibition leads to the pubertal increase in LHRH release, hence the onset of puberty. However, there remained a possibility that the reduction of inhibitory GABA tone may increase relative strength of stimulatory glutamate tone. In fact, infusion of the antisense oligo for GAD67 mRNA, which interferes with GAD synthesis, not only stimulated LHRH release, but also increased glutamate release in prepubertal monkeys. Therefore, in this study we examined whether the effects of the antisense oligo for GAD67 mRNA can be altered by simultaneous infusion of the NMDA blocker, MK801 in both prepubertal and pubertal monkeys. While in both groups of monkeys, infusion of the antisense oligo for GAD67 mRNA at 1 M into the S-ME alone stimulated LHRH release, simultaneous infusion of MK801 at 5 M and the antisense oligo did not result in elevated LHRH release. Infusion of MK801 alone did not cause any significant effects. The results indicate that infusion of MK801 blocks the LHRH release induced by the antisense oligo for GAD67 mRNA in both prepubertal and pubertal monkeys. The data are further interpreted to mean that the increased LHRH release with the antisense oligo for GAD67 mRNA may be partly due to an increase in glutamate tone mediated by NMDA receptors, as well as to the decrease in GAD synthesis and subsequent decrease in GABA release. FUTURE DIRECTIONS We will examine the further relationship between the decrease in GABA and the increase in glutamate in puberty. KEY WORDS GABA, glutamate, NMDA receptors, puberty